The invention relates generally to a method and composition for preventing and/or treating acetaminophen toxicity in a person who has received or is receiving an excessive amount of acetaminophen.
Acetaminophen, or N-acetyl-p-amino phenol, ##STR1##
is a well-known and reliable analgesic commonly used and available without prescription in the United States. Acetaminophen can cause serious damage to liver cells and tissues when an excessive amount is taken. The amount that can lead to this damage varies for individuals based on various factors; for example, lower body weight, past alcoholism, ingestion of acetaminophen with alcohol, or other special sensitivity all can lead to damage from ingestion of amounts of acetaminophen normally not excessive. According to the United States Poison Control Center, thousands of cases of acetaminophen toxicity are reported in the U.S. each year.
Acetaminophen is thought to be metabolized in the liver by cytochrome P-450 enzymes, resulting in highly reactive oxygen free radicals and toxic metabolites, e.g., N-acetyl-.rho.-benzoquinone imine. These metabolites interact with cellular lipids, protein, DNA, and biological macromolecules, causing cell injury and death. When acetaminophen is taken in a non-excessive amount, these metabolites are cleared by hepatic glutathione stores. Excessive amounts of acetaminophen are thought to deplete these glutathione stores, resulting in hepatic necrosis.
Present methods of treating acetaminophen overdose include induction of vomiting, stomach lavage, and/or administration of acetylcysteine to replenish hepatic glutathione. These methods, while somewhat effective in preventing injury if performed within 24 hours of ingestion of the excess amount, are not preventative measures that can inhibit toxicity from the initial time of ingestion. These methods also usually require assistance of medical personnel, which might not be immediately available, particularly because acetaminophen is available for use without a prescription.
There remains a need for an effective method to prevent and/or reduce acetaminophen toxicity in a convenient manner, without need for medical supervision or assistance. The present invention fulfills this need and provides further related advantages.